Impaired ambulation and steroid therapy impact negatively on bone health in multiple sclerosis.

BACKGROUND AND PURPOSE: The prevalence of osteopenia and osteoporosis is higher amongst patients with multiple sclerosis in comparison with the general population. In addition to the general determinants of bone health, two factors may contribute to reduced bone mineral density in multiple sclerosis: physical disability and corticosteroid therapy. The aim of this study was to examine the effect of physical disability and steroid exposure on bone health in weight-bearing bones and spine and on the incidence of low-trauma fractures in multiple sclerosis. METHODS: In this retrospective analysis of prospectively collected data, associations between bone mineral density (at the femoral neck, total femur and the lumbar spine) and its change with disability or cumulative steroid dose were evaluated with random-effect models adjusted for demographic and clinical determinants of bone health. The incidence of low-trauma fractures during the study follow-up was evaluated with Andersen-Gill models. RESULTS: Overall, 474 and 438 patients were included in cross-sectional and longitudinal analyses (follow-up 2347 patient-years), respectively. The effect of severely impaired gait was more apparent in weight-bearing bones (P ≤ 10(-15) ) than in spine (P = 0.007). The effect of cumulative steroid dose was relatively less pronounced but diffuse (P ≤ 10(-4) ). Risk of low-trauma fractures was associated with disability (P = 0.02) but not with cumulative steroid exposure and was greater amongst patients with severely impaired gait (annual risk 3.5% vs. 3.0%). Synergistic effects were found only between cumulative steroid dose in patients ambulatory without support (P = 0.02). CONCLUSIONS: Bone health and the incidence of low-trauma fractures in multiple sclerosis are more related to impaired gait than to extended corticosteroid therapy.

Recurrent Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1 Syndrome.

Primary hyperparathyroidism is a common endocrinopathy. Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare autosomal dominantly inherited endocrine tumor predisposition syndrome, with one of main manifestations being primary hyperparathyroidism. We retrospectively evaluated a set of 1011 patients who underwent surgery for primary hyperparathyroidism between the years 2018-2022, and found 78 (8 %) patients who underwent reoperations and 27 patients with MEN1 syndrome. In the group of patients with MEN1 syndrome, 7 (35 %) needed reoperations. Patients with multiple endocrine neoplasia syndrome have a higher risk of needing reoperation. Genetic testing can help identify MEN1 syndrome preoperatively and to better evaluate the approach to surgery.

Effects of morning vs. evening teriparatide injection on bone mineral density and bone turnover markers in postmenopausal osteoporosis.

UNLABELLED: A 12-month morning teriparatide (TPTD) administration resulted in a larger increase in the lumbar spine bone mineral density (BMD) than the evening application. The results indicate that the response of bone cells to teriparatide treatment depends on dosing time. INTRODUCTION: The aim of this study was to assess the long-term effects of the morning vs. the evening teriparatide administration on BMD and bone turnover markers (BTMs) in postmenopausal osteoporosis. METHODS: Fifty women with established postmenopausal osteoporosis were randomized to 12-month treatment with 20 µg of TPTD, administered daily in the morning or in the evening. The BMD and serum concentrations of C-terminal telopeptide of type I collagen, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) were measured at baseline, after 6 and 12 months. General linear model-repeated measurements were used to analyze the data. RESULTS: After 12 months, the lumbar spine BMD grew markedly (p < 0.001) with a significantly greater increase in the morning arm compared to the evening arm (9.1% vs. 4.8%, respectively, p < 0.05). The BMD at the distal radius significantly decreased (p < 0.001), with no differences between the arms. The BMD at proximal femur did not change significantly. After 6 months, the BTMs were significantly increased compared with baseline (p < 0.001). The increases in the evening arm vs. the morning arm, however, were more pronounced in PINP (+358% vs. +215%, respectively) and in TRAP 5b (+70% vs. +37%, respectively) (both p < 0.05). CONCLUSION: 12-month morning administration of TPTD resulted in a larger increase in the lumbar spine BMD than the evening application. The timing of TPTD administration may be important for its efficacy.

Plasma concentrations of fibroblast growth factors 21 and 19 in patients with Cushing's syndrome.

The objective of this study was to measure plasma fibroblast growth factor 21 and 19 (FGF21 and FGF19) levels in patients with Cushing's syndrome (CS) and to compare it with those of lean control subjects (C) and patients with obesity (OB). Fourteen untreated patients with CS, 19 patients with OB and 36 controls were included in the study. Plasma FGF21 and FGF19 levels were measured by ELISA kits, other hormonal and biochemical parameters were measured by standard laboratory methods. Plasma FGF19 did not significantly differ among the studied groups. Plasma FGF21 levels were significantly higher in both CS and OB groups relative to C group but they did not differ between CS and OB groups. In a combined population of all three groups FGF21 levels positively correlated with BMI, waist circumference and percentage of total and truncal fat mass. Less prominent inverse relationship with these parameters was found for FGF19. Neither FGF21 nor FGF19 were significantly related to cortisol concentrations. Increased FGF21 concentrations in both patients with CS and OB relative to lean subjects suggest that excessive body fat and/or related metabolic abnormalities rather than direct effects of cortisol are responsible. In contrast neither obesity nor hypercortisolism significantly affected FGF19 concentrations.

[Glucocorticoids and osteoporosis]. / Glukokortikoidy a osteoporóza.

Treatment with glucocorticoids (GC) has no alternative in many medical disciplines for their anti-inflammatory and immunosuppressive effect. However, osteoporosis and the related fractures are a serious complication brought about by long-term GC therapy. The risk of fractures, especially of the vertebras and the ribs, becomes higher as early as in the first months of oral GC therapy. It grows in proportion to the daily dose of GC, and is present even if low doses are administered (2.5-7.5 mg of prednisone per day). Decreasing bone density (BMD) is not accountable for the higher risk of fractures in GC therapy and fractures occur with higher values of BMD than in primary osteoporosis. There is still no tool that we could use to quantify the changes in the bone quality and the increased risk of fracture in clinical practice. The principal mechanism by which GC induces osteoporosis is inhibition of bone formation caused by the suppression of osteoblastogenesis as well as the activity of functional osteoblasts, with accelerated osteocyte and osteoblast apoptosis. There are significant differences between individuals in terms of GC sensitivity, the reasons of which have not yet been explained. Prior to planned long-term GC therapy (> 3 months) with daily doses higher than 2.5 mg of prednisone p.o. (or higher doses of inhaled GC), it is recommended to perform a densitometry exam using dual-energy X-ray absorptiometry (DXA) in the lumbar region of the spine and femoral collum to evaluate additional risk factors of osteoporosis and fractures for a more precise estimate of the risk of fracture in the specific patient. Sufficient intake of calcium (1,000-1,500 mg of elementary calcium per day) and of the vitamin D (800 IU per day) should be assured in all patients treated by GC. Endogenous production of sexagens should be evaluated and possible substitution therapy should be considered in premenopausal women and younger men. Today, bisphosphonates can be given to patients with a high risk of fracture, the effects of which in preventing the decrease of BMD and vertebral fractures have been documented in randomised clinical studies, even though the evaluation of the risk of fractures was not the primary endpoint of those studies. However, in view of the antiremodelling effect of bisphosphonates, it is clear that this therapy does not eliminate the cause of GC induced osteoporosis and drugs with stimulating effect on osteoblasts will certainly be preferred in the future. Very promising are the first clinical studies of injection parathormone (PTH 1-34) which stimulated bone formation in a continuing GC treatment.

Body composition is associated with bone and glucose metabolism in postmenopausal women with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is associated with increased fracture risk; the underlying mechanism remains unexplained. This study aimed to investigate the relationships between body composition and bone and glucose metabolism in postmenopausal women with T2DM. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) and body composition. A total of 68 postmenopausal women with T2DM and 71 controls were eligible for the study. In contrast to normal BMD in T2DM, a similar prevalence of low-trauma fractures was observed in both groups. T2DM women had significantly higher Trunk fat% and A/G ratio and significantly lower Legs LM% and Legs FM%. Legs LM% was significantly lower in fractured T2DM group and negatively correlated with glycaemia and HbA1c (p<0.01). Serum osteocalcin was significantly lower in T2DM and inversely correlated with FM%, Trunk FM% and A/G ratio (p<0.01) and positively correlated with Legs FM% and total LM% (p<0.05). In conclusion, abdominal obesity and decrease in muscle mass may contribute to low bone formation in T2DM women. Further research is needed to unravel underlying pathophysiological mechanisms and to determine whether maintenance of muscle mass, especially in the lower extremities and/or reduction of central fat mass can prevent fractures.

Inflammatory markers in primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-alpha and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-alpha (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71-1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35+/-1.42 vs. 5.97+/-1.29 10(9) l); APA vs. IHA: TNF-alpha (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63-1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37+/-1.41 vs. 5.71+/-1.21 10(9) l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] microg/l, p

Biochemistry of drugs XXIII. Substance with antineoplastic acitivity LX. Pharmacokinetics of cis-beta-4-pentoxybenzoyl-beta-bromoacrylic acid (cis: Br, H)-3H (Penberol-3H).

After oral administration of Penberol-3H to mice with mammary gland adenocarcinoma HK, within 4 days 50% of the administered radioactivity was excreted in the urine, and 36% in the faeces. In dogs the excretion rates were slower. It was found that after oral administration of Penberol-3H to rats, radioactivity was excreted in the bile. After oral administration of Penberol-3H to mice with mammary gland adenocarcinoma, high specific radioactivities (per gram of tissue) were found in the liver, kidneys, lungs, and ovaries. Besides, it was found that after oral administration of Penberol-3H to nursing female rats the radioactivity was little eliminated in the milk, and in pregnant females its penetration into the fetuses was negligible.

[Acute biochemical effects of calcium: comparison of two dosage forms of calcium carbonate (powder and effervescent tablets) and milk in healthy women]. / Akutní biochemické úcinky vápníku: srovnání dvou ruzných lékových forem uhlicitanu vápenatého (prásek a effervescentní tableta) a mléka u zdravých zen.

BACKGROUND: The aim of this study was to assess acute biochemical changes after the administration of two different pharmaceutical forms of calcium carbonate or milk. METHODS AND RESULTS: The group of 12 young (aged 20-27 years) and 12 older women (aged 63-71 years). After overnight fasting, each of the volunteers received a 1 g of elemental calcium in either form of the tested preparation: powder form of calcium carbonate--Vitacalcin pulvis (Slovakofarma, SR) or effervescent tablet--Calcium 500 mg Pharmavit (Pharmavit, MR) or in 250 ml of milk enriched with the milk calcium complex. Between each test the interval of 1-2 weeks was held. Samples of blood and urine were taken in the fasting state before and during 5.5 h following ingestion of the calcium load. Both calcium carbonate and milk induced a significant increase in the serum ionised calcium (iCa) and a significant decrease in plasma parathormone level (PTH) in comparison with the baseline levels in both groups of women. Comparison between individual preparations and between preparations and milk did not reveal any significant differences in suppression of PTH. Comparison of the effects between young and elderly women did not show any statistically significant difference in any measured parameter. CONCLUSIONS: Our results confirmed the good bioavailability of calcium from milk and from both calcium preparations in both age groups of women. Significantly more frequent hypercalcemia in the young women (p < 0.05) and also the slightly higher hypercalciuria occurred after the application of calcium in the pharmaceutical form of effervescent tablet than after the application of calcium in the form of powder or after the application of milk.

[X-ray densitometry and ultrasonography of the heel bone--sensitivity and comparison with densitometry of the axial skeleton]. / Rentgenová denzitometrie a ultrasonometrie patní kosti--presnost a srovnání s denzitometrií osového skeletu.

BACKGROUND: The aim of the study was to determine the relationship between dual energy x-ray absorptiometry (DXA) and quantitative ultrasonometry (QUS) of calcaneus and their correlation with axial bone mineral density. METHODS AND RESULTS: 1284 subjects were tested for BMD (Bone Mineral Density) by DXA at the spine and hip (707 subjects by DPX-L, Lunar, and 577 subjects by QDR-4500 A, Hologic) and calcaneus (by PIXI, Lunar). The calcaneus was also measured using the QUS (Achilles Plus, Lunar), on the same day. The mean age of the patients was 56.5 +/- 11.6 years, mean height 166 cm, mean weight 70 kg. Three subjects were selected for precision error measurement with low, medium and high BMD of calcaneus (T-score of -2.2, -0.77 and 2.02, respectively) and scanned with re-positioning at the right heel (PIXI and Achilles Plus) 21 times on one day for short term precision error and over 21 consecutive days for long term precision error. The in vivo short term precision error of the heel measurement (BMD, SOS, BUA) in subjects with normal BMD was 0.67%, 0.47% and 1.87%, respectively; the long term in vivo precision error was 1.14%, 0.26% and 2.95%, respectively. No significant difference was found between BMD values on the right and left heel. A statistically significant correlation (p < 0.001) was found between BUA and BMD (r = 0.71), SOS and BMD (r = 0.73), Stiffness and BMD (r = 0.77). The heel BMD was also significantly correlated to BMD of the femoral neck (r = 0.64) and BMD of total femur (r = 0.70) and BMD of lumbar spine (r = 0.59). CONCLUSIONS: The DXA of the heel underestimates the prevalence of osteoporosis. The results of the heel QUS (Stiffness) appear to be better correlated to femoral BMD than heel BMD. The observed correlation coefficient of 0.77 between QUS and DXA at the heel was statistically significant, but it explains only 60% of variability of the QUS of the heel.

Preadipocyte factor-1 concentrations in patients with anorexia nervosa: the influence of partial realimentation.

Preadipocyte factor-1 (Pref-1) is a member of epidermal growth-factor like family of proteins that regulates adipocyte and osteoblast differentiation. Experimental studies suggest that circulating Pref-1 levels may be also involved in the regulation of lipid and glucose metabolism and energy homeostasis. We hypothesized that alterations in Pref-1 levels may contribute to the ethiopathogenesis of anorexia nervosa or its underlying metabolic abnormalities. We measured Pref-1 concentrations and other hormonal, biochemical and anthropometric parameters in eighteen patients with anorexia nervosa and sixteen healthy women and studied the influence of partial realimentation of anorexia nervosa patients on these parameters. The mean duration of realimentation period was 46±2 days. At baseline, anorexia nervosa patients had significantly decreased body mass index, body weight, body fat content, fasting glucose, serum insulin, TSH, free T4, leptin and total protein. Partial realimentation improved these parameters. Baseline serum Pref-1 levels did not significantly differ between anorexia nervosa and control group (0.26±0.02 vs. 0.32±0.05 ng/ml, p=0.295) but partial realimentation significantly increased circulating Pref-1 levels (0.35±0.04 vs. 0.26±0.02 ng/ml, p<0.05). Post-realimentation Pref-1 levels significantly positively correlated with the change of body mass index after realimentation (r=0.49, p<0.05). We conclude that alterations in Pref-1 are not involved in the ethiopathogenesis of anorexia nervosa but its changes after partial realimentation could be involved in the regulation of adipose tissue expansion after realimentation.

Bone mineral density and body composition in men with multiple sclerosis chronically treated with low-dose glucocorticoids.

The aim of the study was to compare the bone mineral density (BMD) and body composition between ambulatory male MS patients and control subjects and to evaluate the relationships among body composition, motor disability, glucocorticoids (GC) use, and bone health. Body composition and BMD were measured by dual-energy X-ray absorptiometry in 104 ambulatory men with MS (mean age: 45.2 years) chronically treated with low-dose GC and in 54 healthy age-matched men. Compared to age-matched controls, MS patients had a significantly lower total body bone mineral content (TBBMC) and BMD at all measured sites except for the radius. Sixty five male MS patients (62.5 %) met the criteria for osteopenia and twenty six of them (25 %) for osteoporosis. The multivariate analysis showed a consistent dependence of bone measures (except whole body BMD) on BMI. The total leg lean mass % was as an independent predictor of TBBMC. The Expanded Disability Status Scale (EDSS), cumulative GC dose and age were independent determinants for BMD of the proximal femur. We conclude that decreasing mobility in male MS patients is associated with an increasing degree of osteoporosis and muscle wasting in the lower extremities. The chronic low-dose GC treatment further contributes to bone loss.

Plasma concentrations of adipocyte fatty acid binding protein in patients with Cushing's syndrome.

Serum adipocyte fatty acid-binding protein (FABP-4) concentrations are linked to human obesity and other features of metabolic syndrome. Patients with Cushing´s syndrome (CS) develop numerous features of metabolic syndrome due to chronic cortisol excess. Here we tested the hypothesis that chronically increased cortisol levels in CS patients may alter circulating levels of FABP-4. Fourteen patients with CS, 19 patients with simple obesity (OB) and 36 healthy control subjects (C) were included in the study. Serum FABP-4 concentrations were significantly higher in both CS and OB patients relative to C group, but they did not differ between CS and OB groups. In a combined population of all groups, serum FABP-4 levels correlated positively with BMI, body fat content, serum glucose, triglycerides, HbA1c and HOMA index and were inversely related to HDL-cholesterol, resting energy expenditure and freeT3 levels. We conclude that FABP-4 levels are significantly increased in both patients with simple obesity and obese patients with Cushing´s syndrome. We suggest that increased FABP-4 concentrations in CS patients are rather due to their excessive fat accumulation and related metabolic abnormalities than due to a direct effect of cortisol on FABP-4 production.

[5,6-bis-(3-alkoxy-carbonyl thio-ureido) benzimidazoles with anthelmintic activity]. / 5,6-bis(3-alkoxykarbonylthioureido) benzimidazoly s anthelmintickou úcinností.

The reaction of potassium thiocyanate with the methyl- and ethyl esters of chloroformic acid (V-VI) in acetone resulted in methoxy- and ethoxycarbonylisothiocyanates which were converted without isolation by means of an addition reaction with 2-alkyl-5,6-diaminobenzimidazoles (I-IV) into the pertinent 2-alkyl-5,6-bis (3-alkoxycarbonyl-2-thioureido) benzimidazoles (VII-XV). The substances obtained were tested for anthelmintic and anticoccidial effectiveness. In anthelmintic screening, substances VIII, IX, XI, XII, XIV and XV were significantly effective against the taenia Hymenolepis nana.

Diminished acute response of osteoclasts to calcium load in thyroidectomized patients.

To elucidate the role of endogenous calcitonin (CT) in the regulation of bone resorption, we evaluated the acute effects of an intravenous calcium load in nine patients after total thyroidectomy (aged 29.2 +/- 8 years) compared with nine healthy subjects. After overnight fasting, intravenous infusions of elemental calcium 1.7 mg/kg body weight were given over a 10-minute period. Blood samples for measurements of serum ionized calcium (S-iCa), plasma intact CT, parathyroid hormone (PTH), and plasma type I collagen cross-linked C-terminal telopeptide (beta-CTX) were obtained 3 minutes before and at 13, 30, 60, 90, and 150 minutes after the start of the infusion. At baseline, parameters of calcium and bone metabolism were similar in both groups. A similar increase in S-iCa and decrease in plasma PTH levels were observed in both groups. However, the plasma CT increased significantly by 13 minutes (P < 0.05) and beta-CTX decreased significantly as early as 30 minutes (P < 0.05) (decrease by 36% as compared with the baseline) only in the group consisting of healthy individuals. In the thyroidectomized group, the plasma beta-CTX did not decrease significantly during the first 60 minutes (decrease by only 8% as compared with the baseline) and response to the calcium load was significantly diminished throughout the study period as compared with that of the healthy subjects (P < 0.01). In conclusion, the results indicate that the increased CT secretion is responsible for the rapid initial decrease in the bone resorption following an acute intravenous calcium load.

[Derivatives of thioallophanic acid with anthelmintic activity]. / Deriváty thioallofanové kyseliny s anthelmintickou úcinností.

A reaction of potassium thiocyanate with methyl and ethyl ester of chloroformic acid (I-II) resulted in methoxy- and ethoxycarbonyl isothiocyanates which through an addition reaction with various primary and secondary amines, diamines and hydrazines yielded the perinently substituted esters of thioallophanic acid (III-XXI). The obtained agents were tested for anthelmintic and anticoccidial effects.

[Effectiveness of phosphonoformic acid in herpes infections]. / Ucinnost kyseliny fosfonomravencí na herpetická onemocnení.

The antiviral efficacy of phosphonoformic acid (PFA) was examined on tissue cultures of the human embryonal lungs against the viruses herpes simplex type 1 and 2, herpes zoster, and the human cytomegalovirus using the method of the inhibition of the cytopathic effect and against herpes simplex type 1 and 2 on the tissue cultures of Vero cells using the methods of the inhibition of plaque formation. PFA was demonstrated to inhibit the reproduction of the viruses under study in both tests on tissue cultures. In persistence studies, the cytomegalovirus was not isolated back from the cells of the human embryonal lungs, which gave evidence of its greater sensitivity to PFA. In in vivo experiments, PFA in the form of a 3% ointment suppressed herpetic dermatitis on the guinea-pig skin, when treatment started 6, 24 and 48 hours after infection. In a preliminary experiment on rabbit corneas, an ointment with 3% PFA inhibited herpetic keratoconjunctivitis in time intervals of 1 and 3 hours after infection.